The overall goal of this proposal is to determine what changes take place in the structure of dentate granule neurons during the adult portion of the lifespan of the rat. Specifically, the proposed studies will determine: 1) whether or not changes occur in granule cell axons and their local collaterals as the animal ages, 2) if there is a pattern to age-related morphological changes in either dendrites or axons, and 3) if the structural differences which are seen between early and late-generated neurons in young adults persist throughout life. The dentate gyrus is the first stage in the flow of information through the hippocampal formation. It has been studied extensively in older rodents and primates in an attempt to understand the mechanisms responsible for the functional decline in short term memory which occurs during aging. Although there are now reports showing morphological changes in granule neurons from aged animals, the above issues regarding axon and dendritic structure have not been addressed. The proposed studies will make use of intracellular labeling with horseradish peroxidase, wholemounts of in vitro slices, and a computer-microscope system to analyze, in three dimensions, dentate granule neurons from rats of six age groups between 6 and 36 months. Only those neurons with completely filled processes will be analyzed and, for each neuron, a number of parameters will be quantified, including lengths, diameters and numbers of dendritic segments and axonal collaterals, axonal trajectories, numbers and distribution of axonal swelling, and dendritic spine density. Comparisons of these parameters between animals of different age groups will then be done in order to resolve the issues discussed above.